DESCRIPTION: (Applicant's Abstract) The long-term goal of this project is to investigate the regulatory effects of serotonin on fast sensory synaptic transmission in the spinal cord. Spinal nociceptive transmission receives the control of endogenous pain modulatory systems in the central nervous system. Descending serotonergic projecting pathways from the rostroventral medulla play important roles in the modulation of spinal nociceptive transmission. However, synaptic mechanisms of serotonergic inhibition and facilitation in the spinal cord are not completely understood. In this proposal, the regulation of spinal fast synaptic transmission by serotonin will be studied. To characterize AMPA and kainate receptor-mediated sensory synaptic transmission in the spinal dorsal horn, fast glutamatergic synaptic transmission between primary afferent fibers and spinal dorsal horn neurons will be examined using whole-cell patch-clamp recording techniques in spinal cord slices. Pharmacological receptor antagonists will be used to examine kainate receptor-mediated EPSCs. AMPA and kainate receptor-mediated currents will be also recorded from isolated or cultured dorsal horn neurons. To examine the role of kainate receptors in ascending sensory transmission, kainate receptor-mediated EPSCs induced by stimulation of afferent sensory fibers will be studied. Recordings from prelabeled spinothalamic tract cells will be also performed. Experiments will be carried out to investigate the effects of 5-HT on kainate receptor-mediated EPSCs and agonist-evoked currents. Finally, pharmacological experiments will be performed to study synaptic mechanisms for facilitation produced by 5-HT, in spinal slices, isolated or cultured neurons. The proposed studies will generate synaptic mechanisms for fast glutamatergic transmission as well as 5-HT regulation in the spinal cord. This information will be important for understanding central pain transmission and modulation.